Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| INV-002098 | Other Grant/Funding Number | Bill & Melinda Gates Foundation |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Malaria Research and Training Center, Bamako, Mali | OTHER |
| Radboud University Medical Center | OTHER |
Not provided
Not provided
Not provided
The purpose of this study is to assess the gametocytocidal and transmission reducing activity of pyronaridine-artesunate (PA) and dihydroartemisinin-piperaquine (DP) with and without a single low dose of primaquine (PQ; 0.25mg/kg). Outcome measures will include infectivity at 2 and 7 days after treatment, the duration of infectivity in the artemisinin combination therapy (ACT) only arms, and the production and detectability of histidine rich protein II.
Protocol will be shared on request
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pyronaridine-artesunate (PA) | Active Comparator | Subjects will receive pyronaridine-artesunate (PA) once daily for 3 days. |
|
| PA with single low dose primaquine (PQ) | Experimental | Subjects will receive pyronaridine-artesunate (PA) once daily for 3 days, and a low dose of primaquine (PQ) on the first dat of treatment. PQ dose is at the World Health Organization (WHO) recommended dose of 0.25 mg/kg. |
|
| Dihydroartemisinin-piperaquine (DP) | Active Comparator | Subjects will receive dihydroartemisinin-piperaquine (DP) once daily for 3 days. |
|
| DP with single low dose primaquine (PQ) | Active Comparator | Subjects will receive dihydroartemisinin-piperaquine (DP) once daily for 3 days., and a low dose of primaquine (PQ) on the first dat of treatment. PQ dose is at the World Health Organization (WHO) recommended dose of 0.25 mg/kg. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pyronaridine Tetraphosphate/Artesunate | Drug | Adults: Tablets containing 180 mg pyronaridine-tetraphosphate/60mg artesunate (Pyramax, Shin Poong Pharmaceutical Co.), administered according to weight. Children: Granules containing 60 mg pyronaridine-tetraphosphate/20mg artesunate, administered according to weight. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in mosquito infectivity assessed through membrane feeding assays (day 2) | The proportion of mosquitoes infected, assessed through membrane feeding and measured as oocyst prevalence in mosquitoes dissected on day 2 post feed, compared to baseline | 2 days (day 0 & 2) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in mosquito infectivity assessed through membrane feeding assays (day 7) | The proportion of mosquitoes infected, assessed through membrane feeding and measured as oocyst prevalence in mosquitoes dissected on day 7 post feed, compared to baseline | 2 days (day 0 & 7) |
| Mosquito infectivity assessed through membrane feeding assays - inter arm |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Malaria Research and Training Centre | Bamako | Mali | ||||
| Radboud university medical center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35028628 | Derived | Stone W, Mahamar A, Sanogo K, Sinaba Y, Niambele SM, Sacko A, Keita S, Youssouf A, Diallo M, Soumare HM, Kaur H, Lanke K, Ter Heine R, Bradley J, Issiaka D, Diawara H, Traore SF, Bousema T, Drakeley C, Dicko A. Pyronaridine-artesunate or dihydroartemisinin-piperaquine combined with single low-dose primaquine to prevent Plasmodium falciparum malaria transmission in Ouelessebougou, Mali: a four-arm, single-blind, phase 2/3, randomised trial. Lancet Microbe. 2022 Jan;3(1):e41-e51. doi: 10.1016/S2666-5247(21)00192-0. |
Not provided
Not provided
Anonymised individual participant data may be shared on a digital repository or upon reasonable request
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is a single blind randomised controlled trial. The treating physician and staff involved with assessing all laboratory outcomes of the study are blinded, but no placebo will be used. The study pharmacist will be unblinded and responsible for randomisation and treatment administration.
|
|
| Dihydroartemisinin/Piperaquine | Drug | Tablets containing 40 mg dihydroartemisinin/320 mg piperaquine tablets (Eurartesim, Sigma Tau), administered according to weight. |
|
|
| Primaquine Diphosphate | Drug | Extemporaneous preparation of 1mg/mL primaquine phosphate solution, from tablets containing 30mg primaquine (A-PQ 30®, ACE pharmaceuticals, NL) dissolved in 30mL water with a non-interacting fruit-flavoured syrup. Solution will be given at 0.25mg/kg. |
|
|
Mosquito infection prevalence and density, assessed through membrane feeding and measured as oocyst prevalence/density in mosquitoes dissected on day 2 and 7 post feed, compared between study arms |
| 3 days (day 0, 2 & 7) |
| Duration of infectivity | Non PQ arms only: Duration of infectivity will be determined from measures of mosquito infection prevalence, assessed through membrane feeding and measured as oocyst prevalence in mosquitoes dissected on day 0, 2, 7, 10 and 14 post treatment, and then weekly until 2 sequential negative feeds or until day 49. | 5-10 days (as described) |
| Area under the curve (AUC) of infectivity/time | Non PQ arms only: AUC will be determined from measures of mosquito infection prevalence and density, assessed through membrane feeding and measured as oocyst prevalence/density in mosquitoes dissected on day 0, 2, 7, 10 and 14 post treatment, and then weekly until 2 sequential negative feeds or until day 49. | 5-10 days (as described) |
| Haemoglobin level | Haemolysis will be monitored by measuring haemoglobin levels (g/dL) on days 0, 1, 2, 7, 10, 14, 21, 38, 35, 42 and 49 post treatment. | 11 days |
| Histidine rich protein 2 (HRP2) concentration | Histidine rich protein 2 (HRP2) protein concentration in plasma will be determined in subsequent lab analysis from samples collected on days 0, 1, 2, 7, 10, 14, 21, 38, 35, 42 and 49 post treatment. | 11 days |
| Histidine rich protein 2 (HRP2) circulation time | Histidine rich protein 2 (HRP2) protein circulation time will be compared between methods of detection | 11 days |
| Histidine rich protein 2 (HRP2) area under the curve (AUC) | Histidine rich protein 2 (HRP2) area under the curve (AUC) will be determined from measures of HRP2 concentration | 11 days |
| Rapid diagnostic test result | Varied rapid diagnostic tests based on the detection of HRP2 will be used on days 0, 1, 2, 7, 10, 14, 21, 38, 35, 42 and 49 post treatment to determine infection prevalence, for comparison between study arms. | 11 days |
| Gametocyte density | Gametocyte density (parasites/microlitre) will be measured by microscopy and by molecular methods on days 0, 1, 2, 7, 10, 14, 21, 38, 35, 42 and 49 post treatment. | 11 days |
| Gametocyte under the curve (AUC) | Gametocyte area under the curve (AUC) will be determined from measures of density. | 11 days |
| Gametocyte prevalence | Gametocyte prevalence (parasites/microlitre) will be measured by microscopy and by molecular methods on days 0, 1, 2, 7, 10, 14, 21, 38, 35, 42 and 49 post treatment. | 11 days |
| Gametocyte circulation time | Gametocyte circulation time (days) will be determined from measures of prevalence. | 11 days |
| Gametocyte sex ratio | Gametocyte density will be determined by molecular methods for males and females separately, allowing analysis of sex ratio (proportion of total that is male) on days 0, 1, 2, 7, 10, 14, 21, 38, 35, 42 and 49 post treatment. | 11 days |
| Asexual parasite density | Asexual parasite density (parasites/microlitre) will be measured by microscopy and by molecular methods on days 0, 1, 2, 7, 10, 14, 21, 38, 35, 42 and 49 post treatment. | 11 days |
| Asexual parasite area under the curve (AUC) | Asexual parasite area under the curve (AUC) will be determined from measures of density. | 11 days |
| Asexual parasite prevalence | Asexual parasite prevalence (parasites/microlitre) will be measured by microscopy and by molecular methods on days 0, 1, 2, 7, 10, 14, 21, 38, 35, 42 and 49 post treatment. | 11 days |
| Asexual parasite circulation time | Asexual parasite circulation time (days) will be determined from measures of prevalence. | 11 days |
| Parasite genotype | Parasite merozoite surface protein 2 (MSP2) allelic diversity (presence of distinct alleles) will be determined in subsequent lab analysis from whole blood samples collected at baseline. | 1 day |
| Histidine rich protein gene deletion | Deletion (presence/absence) of the HRP2/3 genes will be determined from whole blood samples collected at baseline. | 1 day |
| Nijmegen |
| Netherlands |
| ID | Term |
|---|---|
| D016778 | Malaria, Falciparum |
| ID | Term |
|---|---|
| D008288 | Malaria |
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C027871 | pyronaridine |
| D000077332 | Artesunate |
| C000712628 | pyronaridine tetraphosphate, artesunate drug combination |
| C039060 | artenimol |
| C034759 | piperaquine |
| D011319 | Primaquine |
| ID | Term |
|---|---|
| D037621 | Artemisinins |
| D017382 | Reactive Oxygen Species |
| D005609 | Free Radicals |
| D007287 | Inorganic Chemicals |
| D009930 | Organic Chemicals |
| D012717 | Sesquiterpenes |
| D013729 | Terpenes |
| D006838 | Hydrocarbons |
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided